STUDIES ON THE ANTISENSE OLIGONUCLEOTIDE CONJUGATE

Four oligonucleotides (15 mer) 13-16 and their conjugates 17-20 in whi ch psoralen was covalently linked to 5' end were synthesized. Compound s 16 and 20 contain the sequence which is complementary to the sense s trand covering the first four codons and the upstream sequence close t o the ribosome binding site of c-Ha-ras mRNA. It was found that compou nds 16 and 20 inhibited the growth of cells that had been transformed by the c-Ha-ras plasmid activated c-Ha-ras oncogene. Compound 20 that carried psoralen was more efficient in inhibiting the growth of transf ormed cells than compound 16 without psoralen, suggesting that the pso ralen might have increased permeability of oligodeoxynucleotides. A mo del experiment of duplex formation was pertinent to the idea that the inhibitory effect was caused by RNase H activity.